A woman with thyrotoxicosis- and hyperemesis gravidarum-associated Wernicke's encephalopathy

Although hyperthyroidism arising from primary thyroid disease is rare in pregnancy, transient gestational hyperthyroidism is not uncommon. This condition can be associated with hyperemesis gravidarum (HG), and Wernicke's encephalopathy. We present the case of a woman with toxic nodular goiter complicating HG-associated Wernicke's encephalopathy. A 38-year-old Caucasian woman, who had received a diagnosis of hyperthyroidism and HG early in her pregnancy, had intrauterine fetal death at Week 16 of gestation. One day after undergoing therapeutic abortion, she was admitted to our clinic with persistent thyrotoxicosis, nausea, and vomiting. A toxic thyroid nodule was detected. She was given antithyroid medication, total parenteral nutrition. On Day 10 of hospitalization, she developed ataxia, aphasia, and somnolence. Cranial magnetic resonance imaging showed increased bilateral thalamic signalization. She was given a diagnosis of Wernicke's metabolic encephalopathy, for which she received thiamine and multivitamin preparations. She responded dramatically on the second day of thiamine therapy. Her consciousness improved rapidly and she began to speak. Her muscle tone was slightly weak and she had paresthesias in both legs. Absorption of thiamine may be particularly impaired in pregnant women with hyperemesis and hyperthyroid disease. Wernicke's encephalopathy should be considered in hyperthyroid women with HG who develop neurological abnormalities.     

Misfolded proteins inhibit proliferation and promote stress-induced death in SV40-transformed mammalian cells

Protein misfolding is implicated in neurodegenerative diseases and occurs in aging. However, the contribution of the misfolded ensembles to toxicity remains largely unknown. Here we introduce 2 primate cell models of destabilized proteins devoid of specific cellular functions and interactors, as bona fide misfolded proteins, allowing us to isolate the gain-of-function of non-native structures. Both GFP-degron and a mutant chloramphenicol-acetyltransferase fused to GFP (GFP-Δ9CAT) form perinuclear aggregates, are degraded by the proteasome, and colocalize with and induce the chaperone Hsp70 (HSPA1A/B) in COS-7 cells. We find that misfolded proteins neither significantly compromise chaperone-mediated folding capacity nor induce cell death. However, they do induce growth arrest in cells that are unable to degrade them and promote stress-induced death upon proteasome inhibition by MG-132 and heat shock. Finally, we show that overexpression of all heat-shock factor-1 (HSF1) and Hsp70 proteins, as well as wild-type and deacetylase-deficient (H363Y) SIRT1, rescue survival upon stress, implying a noncatalytic action of SIRT1 in response to protein misfolding. Our study establishes a novel model and extends our knowledge on the mechanism of the function-independent proteotoxicity of misfolded proteins in dividing cells.     

Use of linear mixed models for genetic evaluation of gestation length and birth weight allowing for heavy-tailed residual effects

Background

The distribution of residual effects in linear mixed models in animal breeding applications is typically assumed normal, which makes inferences vulnerable to outlier observations. In order to mute the impact of outliers, one option is to fit models with residuals having a heavy-tailed distribution. Here, a Student''s-t model was considered for the distribution of the residuals with the degrees of freedom treated as unknown. Bayesian inference was used to investigate a bivariate Student''s-t (BSt) model using Markov chain Monte Carlo methods in a simulation study and analysing field data for gestation length and birth weight permitted to study the practical implications of fitting heavy-tailed distributions for residuals in linear mixed models.

Methods

In the simulation study, bivariate residuals were generated using Student''s-t distribution with 4 or 12 degrees of freedom, or a normal distribution. Sire models with bivariate Student''s-t or normal residuals were fitted to each simulated dataset using a hierarchical Bayesian approach. For the field data, consisting of gestation length and birth weight records on 7,883 Italian Piemontese cattle, a sire-maternal grandsire model including fixed effects of sex-age of dam and uncorrelated random herd-year-season effects were fitted using a hierarchical Bayesian approach. Residuals were defined to follow bivariate normal or Student''s-t distributions with unknown degrees of freedom.

Results

Posterior mean estimates of degrees of freedom parameters seemed to be accurate and unbiased in the simulation study. Estimates of sire and herd variances were similar, if not identical, across fitted models. In the field data, there was strong support based on predictive log-likelihood values for the Student''s-t error model. Most of the posterior density for degrees of freedom was below 4. Posterior means of direct and maternal heritabilities for birth weight were smaller in the Student''s-t model than those in the normal model. Re-rankings of sires were observed between heavy-tailed and normal models.

Conclusions

Reliable estimates of degrees of freedom were obtained in all simulated heavy-tailed and normal datasets. The predictive log-likelihood was able to distinguish the correct model among the models fitted to heavy-tailed datasets. There was no disadvantage of fitting a heavy-tailed model when the true model was normal. Predictive log-likelihood values indicated that heavy-tailed models with low degrees of freedom values fitted gestation length and birth weight data better than a model with normally distributed residuals.Heavy-tailed and normal models resulted in different estimates of direct and maternal heritabilities, and different sire rankings. Heavy-tailed models may be more appropriate for reliable estimation of genetic parameters from field data.     

Compress-store on blockchain: a decentralized data processing and immutable storage for multimedia streaming

Cluster Computing - Decentralization for data storage is a challenging problem for blockchain-based solutions as the blocksize plays a key role for scalability. In addition, specific requirements...     

First record of the Lessepsian fish Siganus rivulatus (Forsskål & Niebuhr, 1775) in the Sea of Marmara (Izmit Bay,Turkey)

The marbled spinefoot, Siganus rivulatus (Forsskål&Niebuhr, 1775) was recorded for the first time in Izmit Bay, Sea of Marmara. One specimen was caught on 30 September 2019 by a small scale fisherman at depth of 25 m. The fish measured 151 mm in total length and weighted of 43.45 g. S. rivulatus is one of the Lessepsian immigrants who entered the Mediterranean more than half a century ago, and has now also easily adapted to the Sea of Marmara, which has a unique two-layered water system.     

Increased lymphocyte deoxyribonucleic acid damage in patients with cardiac syndrome X

OBJECTIVES: To investigate whether there is lymphocyte deoxyribonucleic acid (DNA) damage in patients with cardiac syndrome X (CSX), and its relation with total antioxidant status (TAS), inflammation and ischemia. METHODS: Twenty-three patients with CSX, 21 patients with non-CSX (NCSX) and 20 healthy volunteers were included in the study. Lymphocyte DNA damage (Arbitrary Unit) was assessed by alkaline single cell electrophoresis (comet) assay in peripheral lymphocyte, and plasma levels of TAS (mmol Trolox equiv./l) were determined using a novel automated measurement method. High sensitive C-reactive protein (hsCRP) and other biochemical parameters were measured from all subjects. Treadmill exercise test and coronary angiography were performed to CSX and NCSX groups. RESULTS: Lymphocyte DNA damage was increased in patients with CSX compared with NCSX and control group (p<0.001, for both). Also, TAS was decreased, and hsCRP was increased in CSX compared with NCSX and control group (p<0.001, for all). Lymphocyte DNA damage was correlated with magnitude of ST depression (p=0.034), hsCRP (p=0.001), TAS (p<0.001) and presence of diabetes (p=0.022) in bivariate analysis. In multiple linear regression analysis, lymphocyte DNA damage was correlated with only TAS (beta=-0.413, p=0.017) and hsCRP (beta=0.414, p=0.006). CONCLUSION: Lymphocyte DNA damage was increased in patients with CSX. The increase in lymphocyte DNA damage may be related with increased oxidative stress and inflammation in patients with CSX.     

Determination of degradation of radioactivity and its kinetics in aerobic composting

In this study, the kinetics of disappearance of radioactivity in aerobic composting was investigated. For this purpose, compost materials were prepared by mixing sugar beet wastes, wine factory wastes (grape wastes), straw and biological treatment sludge in different amounts. While alpha-radioactivity was not initially detected in all composting materials, the composting materials had some beta-radioactivity. In the mixtures of sugar beet wastes--straw-biological treatment sludge (1), sugar beet wastes-wine factory wastes (grape wastes)-biological treatment sludge (II) and wine factory wastes (grape wastes)-biological treatment sludge (III), the beta-radioactivity reduced by 82%, 58%, 85% respectively of initial values after 52 d. The beta-radioactivity degradation in the composting process could be represented by first-order kinetics and reaction rate constants of mixtures of I, II and III were k = 0.0693 d(-1) (R2 - 0.84), k = 0.0453 d(-1) (R2 = 0.98), k = 0.0234 d(-1) (R2 = 0.97), respectively.